News & Comment

Angela Nieto received her PhD from Universidad Autónoma in Madrid in 1987. After short postdoctoral stays in Madrid and at the Max Planck Institute for Psychiatry in Munich, she joined the National Institute for Medical Research in London in 1989 and returned to Spain in 1993 to lead a research group at the Cajal Institute. She moved to the Neurosciences Institute in Alicante in 2004 as full professor and head of developmental neurobiology. She currently leads the cell plasticity in health and disease program and coordinates the Spanish National Research Council Cancer Hub.

As we do every December, we revisit the highs and lows of the past year in a dedicated Focus issue of commissioned comment, news and highlights from the primary research literature.

The initial discovery of an inhibitor of KRAS G12C revolutionized the KRAS field. Since then, more-potent G12C-specific inhibitors, newer allele-specific inhibitors and combinations based on KRAS targeting have advanced through clinical trials, which has led to approval by the US Food and Drug Administration of the first KRAS–EGFR inhibition combinations.

Over the past decade, multiple lines of inquiry have converged on the appreciation that the nervous system plays crucial roles in cancer pathophysiology. Key conceptual advances will mark 2025 as a milestone year in which the ‘emerging’ cancer neuroscience field developed into an established field. Here, we discuss the latest developments.

Targeted therapies continue to transform the landscape of non-small-cell lung cancer (NSCLC). In 2025, the US Food and Drug Administration approved two targeted therapies, an antibody–drug conjugate and a tyrosine kinase inhibitor, for specific molecular subtypes of NSCLC. In this Clinical Outlook, we discuss their impact on the field.

Foundation models hold transformative promise for oncology, yet their clinical implementation remains limited, largely owing to their current model design as narrow specialists optimized for static tasks, whereas clinical oncology requires generalist systems capable of integrating multimodal data, capturing disease evolution over time and considering patient perspectives. Design along these requirements is essential to integrating foundation models as trusted partners in cancer care.

Antibiotic-related dysbiosis has emerged as a major, yet potentially modifiable, barrier to immune-checkpoint inhibitor (ICI) efficacy in patients with cancer. Although antibiotic stewardship remains the primary recommendation, the advent of point-of-care microbiome profiling tools and targeted, preventative or restorative interventions may offer strategies to counter antibiotic-related dysbiosis and improve outcomes.

Cancer is causing a global health crisis, straining even wealthy nations with rising cases, costs and workforce limits. Europe lags in translating basic research discoveries into clinical applications. We must invest in prevention, fundamental research, clinical trials, biotech support, workforce and patient involvement to stay competitive.

Bispecific antibodies and ADCs battle for the limelight, CAR-T therapy sees late surge and China’s growth continues.

Fostering a nimble, innovative and resilient biomedical workforce is crucial. Here, we consider how to accelerate the readiness of early career investigators to lead, inverting the traditional pyramid view of academia to place them at the top, with expansive possibilities for advancement.

Investment continues as the field awaits phase 3 readouts for next-generation radioligand therapies in 2026.

Propelled by a growing understanding of nasopharyngeal carcinoma pathogenesis through elucidation of its genomic and immune landscape, therapy has progressed from radiotherapy alone to combined chemotherapy and immunotherapy. This Clinical Outlook focuses on recent milestones and future directions for patients with nasopharyngeal carcinoma.

Ron DePinho received his MD from the Albert Einstein College of Medicine and completed his medical and postdoctoral training at Columbia University. He was the founding director of the Belfer Center at the Dana-Farber Cancer Institute. As president of the University of Texas MD Anderson Cancer Center, he launched the Cancer Moonshot initiative. He currently serves as a professor of cancer biology at the MD Anderson Cancer Center and was elected to the National Academies of Sciences and Medicine. He is the co-founder of several biotech companies and an advocate for innovation-driven healthspan solutions for the underserved.

Ralph DeBerardinis obtained an MD and PhD from the University of Pennsylvania, then trained in Pediatrics and Medical Genetics at Children’s Hospital of Philadelphia. He moved to the University of Texas Southwestern Medical Center (UTSW) in 2008, serving as Chief of Pediatric Genetics and Metabolism from 2013 to 2024. He became an Investigator in the Howard Hughes Medical Institute in 2018 and was elected to the National Academy of Medicine in 2020. DeBerardinis’s current roles at UTSW include directing the Eugene McDermott Center for Human Growth and Development and the Genetic and Metabolic Disease Program in the Children’s Research Institute.